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Introduction and objectives: arrhythmogenic cardiomyopathy (ACM) is a hereditary heart disease defined by the progressive replacement of the ventricular myocardium with fibroadipose tissue, which can act as a substrate for arrhythmias, sudden death, or even give rise to heart failure (HF). Sudden death is frequently the first manifestation of the disease, particularly among young patients. The aim of this study is to describe a new pathogenic variant in the PKP2 gene. Methods: A descriptive observational study that included 8 initially non-interrelated families with a diagnosis of ACM undergoing follow-up at our HF and Familial Cardiomyopathies Unit, who were carriers of the NM_004572.3:c.775_776insG; p. (Glu259Glyfs*77) variant in PKP2 gene. The genetic testing employed next-generation sequencing for the index cases, and the Sanger method for the targeted study with family members. We compiled personal and family histories, demographic and clinical characteristics, data from the additional tests at the time of diagnosis, and arrhythmic events at diagnosis and during follow-up. Results: We included 47 subjects, of whom 8 were index cases (17%). Among the evaluated family members, 16 (34%) were carriers of the genetic variant, 3 of whom also had a diagnosis of ACM. The majority were women (26 patients; 55.3%), with a mean age on diagnosis of 48.9 ± 18.6 years, and a median follow-up of 39 [24-59] months. Worthy of note are the high incidence of arrhythmic events as the form of presentation and in follow-up (21.5% and 20.9% respectively), and the onset of HF in 25% of the sample. The most frequent ventricular involvements were right (4 patients 16.7%) and biventricular (4 patients 16.7%); we found no statistical differences in any of the variables analysed. Conclusions: This variant is a pathogenic variant of gene PKP2 that has not previously been described and is not present in the control groups associated with ACM. It has incomplete penetrance, a highly variable phenotypic expressivity, and was identified in 8 families of our geographical area in Malaga (Andalusia, Spain), where we can establish a founder effect and describe the clinical and risk characteristics.

Pulmonary vein (PV) isolation is a well-established rhythm control therapy in atrial fibrillation (AF). Currently, there is no consensus on which ablation technique to use for the first procedure, cryoballoon (CB) or radiofrequency (RF). A retrospective cohort study was conducted on 1055 patients who underwent a first ablation, to assess both techniques based on the need for reablation. Patients with CB (n = 557) and RF (n = 498) ablations were clinically characterized and the need for reablation during a 30-month follow-up was used as the primary endpoint. Independent variables were analyzed to identify potential predictors. The need for reablation was significantly lower in the CB group than in the RF group (hazard ratio = 0.45 and 95% confident interval = 0.32–0.61; p < 0.001); in both paroxysmal and persistent AF, using a full-adjusted regression Cox model by age, sex, smoking, hypertension, diabetes mellitus, dyslipidemia, severe obstructive sleep apnea, dilated left atrium, persistent AF and early recurrence. RF ablation, dilated left atrium, persistent AF and early recurrence were identified as independent predictors of reablation. In addition, the CB-redo subgroup had a lower PV reconnection than the RF-redo subgroup. In conclusion, CB ablation suggests a reduction in the need for reablation and lower PV reconnection during the follow-up than RF ablation.

ObjectivesThe association between obesity and atrial fibrillation (AF) is well-established. We aimed to evaluate the impact of index body mass index (BMI) on AF recurrence at 12 months following catheter ablation using propensity-weighted analysis. In addition, periprocedural complications and fluoroscopy details were examined to assess overall safety in relationship to increasing BMI ranges.MethodsBaseline, periprocedural and follow-up data were collected on consecutive patients scheduled for AF ablation. There were no specific exclusion criteria. Patients were categorised according to baseline BMI in order to assess the outcomes for each category.ResultsAmong 3333 patients, 728 (21.8%) were classified as normal (BMI 2), 1537 (46.1%) as overweight (BMI 25.5–29.0 kg/m2) and 1068 (32.0%) as obese (BMI ≥30.0 kg/m2). Procedural duration and radiation dose were higher for overweight and obese patients compared with those with a normal BMI (p=0.002 and p2led to a 1.2-fold increased likelihood of experiencing recurrent AF at 12-months follow-up as compared with overweight patients (HR 1.223; 95% CI 1.047 to 1.429; p=0.011), while no significant correlation was found between overweight and normal BMI groups (HR 0.954; 95% CI 0.798 to 1.140; p=0.605) and obese versus normal BMI (HR 1.16; 95% CI 0.965 to 1.412; p=0.112).ConclusionsPatients with a baseline BMI ≥30 kg/m2have a higher recurrence rate of AF following catheter ablation and therefore lifestyle modification to target obesity preprocedure should be considered in these patients.

Introduction and objectives Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty replacement of predominantly right ventricular myocardium . This cardiomyopathy is a frequent cause of sudden cardiac death in young people and athletes. The aim of our study was to determine the incidence of pathological or likely pathological desmosomal mutations in patients with high-risk definite ARVC. Methods This was an observational, retrospective cohort study , which included 36 patients diagnosed with high-risk ARVC in our hospital between January 1998 and January 2015. Genetic analysis was performed using next-generation sequencing . Results Most patients were male (28 patients, 78%) with a mean age at diagnosis of 45 ± 18 years. A pathogenic or probably pathogenic desmosomal mutation was detected in 26 of the 35 index cases (74%): 5 nonsense, 14 frameshift, 1 splice, and 6 missense. Novel mutations were found in 15 patients (71%). The presence or absence of desmosomal mutations causing the disease and the type of mutation were not associated with specific electrocardiographic, clinical, arrhythmic, anatomic, or prognostic characteristics. Conclusions The incidence of pathological or likely pathological desmosomal mutations in ARVC is very high, with most mutations causing truncation. The presence of desmosomal mutations was not associated with prognosis.

Resumen Introduccion y objetivos La miocardiopatia arritmogenica del ventriculo derecho (MCAVD) es una cardiopatia hereditaria definida por la sustitucion progresiva de miocardio ventricular derecho por tejido fibroadiposo. Es causa frecuente de la muerte subita de jovenes atletas. El objetivo del presente estudio es conocer la incidencia de variantes desmosomicas patogenicas o probablemente patogenicas en pacientes con MCAVD definitiva de alto riesgo. Metodos El estudio de cohortes retrospectivo observacional incluyo a 36 pacientes diagnosticados de MCAVD definitiva de alto riesgo en nuestro hospital entre enero de 1998 y enero de 2015. El analisis genetico se realizo con next-generation sequencing. Resultados La mayoria eran varones (28 pacientes, 78%) con una media de edad al diagnostico de 45 ± 18 anos. Se detecto al menos 1 variante desmosomica patogenica o probablemente patogenica en 26 de los 35 casos indice (74%): 5 nonsense, 14 frameshift, 1 splice y 6 missense. En 15 pacientes (71%) se encontraron mutaciones nuevas. La presencia o la ausencia de mutaciones desmosomicas o la naturaleza de estas no se asociaron con caracteristicas electrocardiograficas, clinicas, arritmicas, anatomicas o pronosticas especificas. Conclusiones La incidencia de variantes desmosomicas patogenicas o probablemente patogenicas en MCAVD definitiva de alto riesgo fue muy alta, con mayoria de mutaciones que causan truncamiento. La presencia de mutaciones desmosomicas no se asocio con el pronostico.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC/D) is an inherited cardiomyopathy characterized by ventricular arrhythmias and heart failure. The aim of our study was to analyze the impact of the ICD indication in the prognosis of patients with high-risk ARVC/D according to the consensus document. Methods The high-risk category includes patients who experienced cardiac arrest due to sustained ventricular tachycardia or ventricular fibrillation and patients with severe right or left ventricular dysfunction. We included 41 patients with high-risk ARVC/D: 33 in secondary prevention and 8 in primary prevention. Results We followed 41 patients during 6.37 ± 4.88 years. Twenty-six patients (63.4%) had at least one appropriate arrhythmic event: 24 p (72.7%) in secondary prevention and 2 p (25%) in primary prevention; p=0.02. Twenty-four patients (72.7%) in secondary prevention and five (62.5%) in primary prevention had a cardiovascular event such as arrhythmias, admission due to heart failure, heart transplantation or cardiovascular death. Conclusions High-risk ARVC/D patients had a high number of cardiovascular events, but their nature and treatment were different. Arrhythmic prognosis was worse in secondary prevention and most of the events found in primary prevention were related to heart failure and, therefore, without benefit of the ICD.

Aims Hypertrophic cardiomyopathy is one of the main causes of sudden death in young people. Recent clinical practice guidelines include a risk prediction model for sudden death (HCM Risk-SCD), which facilitates the decision of whether to implant a defibrillator. The aim of our study was to ascertain the percentage of events in our series of primary prevention implantable cardioverter-defibrillator recipients with hypertrophic cardiomyopathy and whether HCM Risk-SCD predicts the onset of arrhythmic events. Methods and results This was an observational, retrospective cohort study, which included 48 primary prevention defibrillator recipient patients with HCM. We compiled their demographic and clinical characteristics, estimated 5-year risk using HCM Risk-SCD, and collected the documentation on arrhythmias during follow-up. The majority was male (66.7%) and mean age at implantation was 44.44 ± 14.46 years. Non-sustained ventricular tachycardia was the most prevalent risk factor (66.67%), followed by a family history of sudden death (47.92%). Mean HCM Risk-SCD was 6.15 ± 5.01%. HCM Risk-SCD was the only factor independently associated with the onset of ventricular tachyarrhythmia, above any other classic risk factor or association [odds ratio = 1.46 (95% confidence interval 1.051–2.013); P = 0.02]. None of the 11 patients estimated as low risk using HCM Risk-SCD suffered any appropriate events ( P < 0.05). Conclusions During an average follow-up of 4 years, 16.67% presented appropriate events (4.16%/year). HCM Risk-SCD predicted the onset of events more suitably than classic risk factors.

Resumen Introduccion y objetivo Realizamos este estudio para conocer si la normalizacion de la funcion ventricular tras terapia de resincronizacion (TRC) es mantenida a largo plazo, y su impacto sobre terapias con desfibrilador (DAI) y mortalidad cardiovascular. Metodos En pacientes con miocardiopatia dilatada idiopatica con DAI-TRC, se analizo la fraccion de eyeccion (FE) basal y tras 6 meses del implante, definiendo un grupo (A) que normalizo la FE (≥ 55%) y un grupo (B) restante, con seguimiento a largo plazo, para conocer la evolucion de la FE en ambos grupos y su impacto clinico-arritmico. Resultados De 47 pacientes incluidos, 10 normalizaron la FE a los 6 meses. Los unicos factores predictores fueron el volumen telesistolico del ventriculo (OR: 0,94; IC 95%: 0,92-0,97) y orificio regurgitante mitral (OR: 0,89; IC 95%: 0,86-0,93). Tras seguimiento ecocardiografico medio de 46 meses los pacientes del grupo A mantuvieron la FE preservada (61 ± 6 vs. 64 ± 6%; p = 0,342), y no presentaron ningun evento arritmico. El grupo B, sin mejoria significativa de la FE, presento mas eventos arritmicos (0 vs. 29,7%; p = 0,039). Ademas, en el grupo A no se registro muerte cardiovascular, frente al grupo B con 12 (0 vs. 32,4%; p = 0,031). Conclusiones La normalizacion de la FE a corto plazo en pacientes con miocardiopatia dilatada idiopatica tras TRC se mantiene en el tiempo, e identifica a pacientes con un excelente pronostico a largo plazo.

Aims Interleukin-2 has a significant antitumor activity in some types of cancer, and has been associated with the development of atrial fibrillation (AF). In addition, IL-2 serum levels in recent onset AF have been related with pharmaceutical cardioversion outcomes. We evaluated the hypothesis that a relationship exists between inflammation and the outcome of catheter ablation of AF. Methods We studied 44 patients with paroxysmal AF who underwent catheter ablation. Patients with structural heart disease, coronary artery or valve disease, active inflammatory disease, known or suspected neoplasm, endocrinopathies, or exposure to anti-inflammatory drugs were excluded. All study participants underwent evaluation with a standardized protocol, including echocardiography, and cytokine levels of interleukin-2, interleukin-4, interleukin-6, interleukin-10, tumour necrosis factor-alpha, and gamma-interferon determination before procedure. Clinical and electrocardiographic follow-up were performed with Holter-ECG at 3, 6 and 12 months in order to know if sinus rhythm was maintained. Results After catheter ablation of the 44 patients included (53 ± 10 years, 27.3% female), all patients returned to sinus rhythm. During the first year of follow-up seven patients (15.9%) experienced recurrence of AF. The demographics, clinical and echocardiographic features, and pharmacological treatments of these patients were similar to those who maintained sinus rhythm. The only independent factor predictive of recurrence of AF was an elevated level of IL-2 (OR 1.18, 95% CI 1.12–1.38). Conclusions High serum levels of interleukin-2, a pro-inflammatory non-vascular cytokine, are associated with the recurrence of AF in patients undergoing catheter ablation.

reference group. They also found that normotensive individuals with preserved eGFR (≥90 ml/min/1.73 m) and moderately high ACR (30 to 299 mg/g) have an elevated risk of all-cause death [5]. The results are very similar to the results of our study. Therefore, to conclude that our results are inconsistent with the results of the previous studies may be the result of an incorrect interpretation of the results from the previous studies. Dr. Kawada requested the authors to add medication profiles for hypertension and diabetes mellitus [1]. We added the prevalence of hypertensive subjects on medication and diabetic subjects on medication in Table 2 of this paper. We are confident that the high risks of outcomes in individuals with preserved eGFR and albuminuria observed in our study reflect a true relationship. However, we agree with some of the comments by Dr. Kawada. We used too many explanatory variables in the multivariate-adjusted Poisson model and we share Dr. Kawada's concerns about type I error (overfitting) [6]. We hope the analyses were performed in the spirit of Dr. Kawada's intent. Finally, we strongly agree with the phrase “keeping a satisfactory number of events for the epidemiological study to keep the validity of the outcome” provided by Dr. Kawada. We appreciate having the opportunity to discuss the problem and we express our deepest gratitude to Dr. Kawada.